Action Points

There were also significant changes in adiponectin as well as body mass index.

Both metformin and changes in diet and exercise made significant changes to the size and types of lipid particles in patients with impaired glucose tolerance, researchers found.

In a subgroup analysis of the Diabetes Prevention Program, patients who were randomized to either metformin or to an intense lifestyle intervention had lower levels of various particles of low-density lipoprotein (LDL) cholesterol, and increases in high-density lipoprotein (HDL) particles (P<0.01), Ronald Goldberg, MD, of the University of Miami, and colleagues reported online in the Journal of Clinical Endocrinology & Metabolism.

"Our findings demonstrate that the same therapies used to slow the onset of diabetes also may help allay the risk of heart disease," Goldberg said in a statement.

Earlier research from the Diabetes Prevention Program has shown that intensive lifestyle changes and metformin both reduce diabetes incidence in patients with impaired glucose tolerance. Both treatments have also been shown to modify lipid profiles in this group of patients.

However, their effects on lipoprotein subfractions -- the size and types of particles that carry various types of cholesterol -- have not been studied.

For their analysis, Goldberg and colleagues looked at data on 1,645 patients in the study who had been randomized to one of three groups: placebo, metformin 850 mg twice daily, or a lifestyle intervention aimed at 7% weight loss using a low-fat diet and at least 150 minutes of physical activity per week.

Using both of these techniques together "provides an uncommon opportunity to corroborate the findings with the two methods and to contribute complementary size and density information on VLDL [very-low-density lipoprotein] and LDL subfraction changes," they wrote.

At baseline, there were no differences between the groups in terms of clinical and metabolic parameters, but at 1 year, patients who were in either of the interventions had significant improvements in glycemia, HOMA-IR, adiponectin, physical activity, saturated fat intake, and other metabolic parameters.

Over one year, the researchers found that both of these interventions led to improvements in lipoprotein subfractions, though changes in diet and exercise appeared to have a more powerful impact.

Specifically, the lifestyle intervention decreased large and buoyant VLDL, small and dense LDL, and small HDL, and raised large HDL (P<0.01 for all), while metformin modestly reduced small and dense LDL and raised small and large HDL (P<0.01), the researchers reported.

For the lifestyle intervention, changes in insulin resistance largely accounted for decreases in large VLDL, while changes in body mass index (BMI) and adiponectin were related to changes in LDL, Goldberg and colleagues wrote.

Adiponectin was also related to changes in large HDL, and BMI was tied to changes in small HDL, they added.

On the other hand, metformin's effects on small HDL were independent of adiponectin, BMI, and insulin resistance, the researchers wrote.

They added that the mechanisms behind the improvements are not completely understood, but they considered several explanations.

For instance, the overproduction of large, buoyant VLDL particles is believed to be a "primary abnormality in insulin-resistant states," they wrote, and studies have shown that weight reduction reverses these abnormalities.

Also, a decline in small dense LDL likely reflects reduced triglyceride-cholesterol ester exchange, favoring the formation of larger buoyant LDL that may be less atherogenic, they said.

They concluded that their findings suggest that interventions to slow the development of diabetes may also slow the progression of atherosclerosis, ultimately diminishing heart disease in this population.